PIOfix-study: effects of pioglitazone/metformin fixed combination in comparison with a combination of metformin with glimepiride on diabetic dyslipidemia.

Author(s): Pfutzner A, Schondorf T, Tschope D, Lobmann R, Merke J, Muller J, Lehmann U, Fuchs W, Forst T

Affiliation(s): Institute for Clinical Research and Development, Mainz, Germany. andreasp@ikfe.de

Publication date & source: 2011-06, Diabetes Technol Ther., 13(6):637-43. Epub 2011 Apr 2.

Publication type: Comparative Study; Multicenter Study; Randomized Controlled Trial

OBJECTIVE: Dyslipidemia in patients with type 2 diabetes is characterized by elevated triglyceride levels, decreased high-density lipoprotein (HDL) cholesterol, and a predominance of small dense low-density lipoprotein (LDL) particles. Also, patients suffer from beta-cell dysfunction, chronic systemic inflammation, increased hormonal visceral adipose tissue activity, and an increased risk of cardiovascular events. The aim of our study was to investigate the effect of a fixed pioglitazone + metformin (PM) combination (vs. glimepiride + metformin [GM]) on diabetic dyslipidemia. RESEARCH DESIGN AND METHODS: A total of 288 type 2 diabetes patients completed this double-blind parallel study (187 men, 101 women; age [mean +/- SD], 59 +/- 10 years; body mass index, 32.6 +/- 5.1 kg/m(2); hemoglobin A1c [HbA1c], 7.3 +/- 0.8%). They were randomized to PM or GM for 6 months. Observation parameters at baseline and end point included HDL, LDL, triglycerides, fasting insulin, fasting glucose, total adiponectin, intact proinsulin, and high-sensitivity C-reactive peptide (hsCRP). RESULTS: HDL increased in the PM group by 0.08 +/- 0.25 mmol/L (GM, -0.01 +/- 0.2.8 mmol/L; P < 0.001 vs. PM), whereas LDL increased in both groups (GM, 0.25 +/- 0.90 mmol/L; PM, 0.29 +/- 0.66 mmol/L; difference not significant between groups). Improvements were seen for triglycerides (PM, -0.47 +/- 1.30; GM, -0.19 +/- 1.39 mmol/L), HbA1c (PM, -0.8 +/- 0.9%; GM, -1.0 +/- 0.9%), and glucose (PM, -1.2 +/- 2.1; GM, -1.2 +/- 2.2 mmol/L). Decreases in fasting insulin (PM, -5.2 +/- 11.9; GM, -0.1 +/- 9.8 muU/mL; P < 0.001 between groups), hsCRP (PM, -0.9 +/- 1.9; GM, 0.0 +/- 1.8 mg/L; P < 0.001), and fasting intact proinsulin (PM, -5.5 +/- 11.1; GM, -0.1 +/- 10.0 pmol/L; P < 0.001) and an increase in adiponectin (PM, +6.8 +/- 6.4 mg/L; GM, +0.7 +/- 2.7 mg/L; P < 0.001) were seen in the PM arm, only. CONCLUSIONS: With comparable glycemic control, the fixed PM combination was more efficacious on HDL cholesterol improvement than the GM combination. Additional positive effects were observed for biomarkers of lipid metabolism, beta-cell function, activity of the visceral adipose tissue, and chronic systemic inflammation.